204274-29-3Relevant articles and documents
Synthesis of optically active 2-substituted azetidine-2-carbonitriles from chiral 1-arylethylamineviaα-alkylation ofN-borane complexes
Nakanome, Nobuhiro,Tayama, Eiji
, p. 23825 - 23837 (2021/07/14)
The base-promoted α-alkylation ofN-((S)-1-arylethyl)azetidine-2-carbonitriles3viaformation of theirN-borane complexes4was investigated. For example, treatment of diastereomerically pure boraneN-((S)-1′-(4′′-methoxyphenyl)ethyl)azetidine-2-carbonitrile complex (1S,2S,1′S)-4bwith 1.2 equivalents of LDA at ?78 °C followed by 1.3 equivalents of benzyl bromide at ?78 °C and warming to room temperature produced α-benzylated (2S,1′S)-5bain 72% yield and (2R,1′S)-5bain 2% yield. A mechanism for this diastereoselective α-alkylation was proposed. Our method enables the production of optically active 2-substituted azetidine-2-carbonitriles, such as α-benzylated (S)-10aand (R)-10a, starting from commercially available (S)-(1-(4-methoxyphenyl)ethyl)amine.
Efficient route to (S)-azetidine-2-carboxylic acid
Futamura, Yasuhiko,Kurokawa, Masayuki,Obata, Rika,Nishiyama, Shigeru,Sugai, Takeshi
, p. 1892 - 1897 (2008/02/03)
A new and efficient route to (S)-azetidine-2-carboxylic acid (>99.9% ee) in five steps and total yield of 48% via malonic ester intermediates was established. As the key step, efficient four-membered ring formation (99%) was achieved from dimethyl (S)-(1′-methyl)benzylaminomalonate by treating with 1,2-dibromoethane (1.5 eq) and cesium carbonate (2 eq) in DMF. Krapcho dealkoxycarbonylation of dimethyl (1′S)-1-(1′-methyl) benzylazetidine-2,2-dicarboxylate, the product of this cyclization procedure, proceeded with preferential formation (2.7:1, 78% total yield) of the desired (2S,1′S)-monoester, with the help of a chiral auxiliary which was introduced on the nitrogen atom. The undesired (2R,1′S)-isomer could be converted to that with proper stereochemistry, by a deprotonation and subsequent reprotonation step. Finally, lipase-catalyzed preferential hydrolysis of the (2S,1′S)-monoester and subsequent deprotection provided enantiomerically pure (S)-azetidine-2-carboxylic acid in a 91% yield from the mixture of (2S,1′S)- and (2R,1′S)-isomers.
Synthesis and X-ray analysis of 1-((1S)-phenylethyl)-azetidine-(2R)-piperidinamide
De Gelder,Smits,Starmans,Thijs,Zwanenburg
, p. 639 - 642 (2007/10/03)
The crystal and molecular structure of a new azetidine-2-carboxylic amide derivative is described. The structure was solved by direct methods and refined by least squares methods to R1 = 0.0393 for 4264 reflections (with I > 2σ(I)). The structure consists
